Imipenem resistance in Enterobacter aerogenes is associated with derepression of chromosomal cephalosporinases and impaired permeability

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Abstract
Enterobacter aerogenes mutants with high-level resistance to imipenem were studied. They were derived from strains characterized by stable overproduction of a class-I β-lactamase. This enzyme (pI= 8.2) exhibited high affinity toward imipenem and hydrolysed the drug slowly. Imipenem-resistant mutants lacked a major 43-kDa outer membrane protein and displayed decreased permeability to cephaloridine. Introduction of a plasmid coding for the regulatory ampD gene abolished β-lactamase production and rendered the mutants susceptible to imipenem.